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<p>Pazopanib, a multitargeted tyrosine kinase inhibitor faces challenges at the formulation forefront due to high melting point, pH-dependent low aqueous solubility, <i>in-vivo</i> precipitation, low dissolution kinetics and, P-gp mediated drug efflux. To address these limitations an amorphous nanosuspension of Pazopanib (PZB-NS) was developed using an antisolvent precipitation approach with a dual stabilizer system comprising polyvinylpyrrolidone K-30 (PVP K-30) and Soluplus®. Formulation optimization was conducted using a Box-Behnken design (BBD) investigating critical process parameters such as polymer and surfactant concentrations, and solvent-to-antisolvent addition rate. The optimized nanosuspension exhibited a particle size of 123.9 ± 3.36&#xa0;nm with 0.121 ± 0.002 PDI. The nano-formulation was further subjected to morphological characterization through PLM, SEM and PXRD that demonstrated amorphous transition of highly crystalline PZB. The FT-IR spectra revealed stabilizer-mediated hydrogen bonding and hydrophobic interactions while TEM micrographs depicted the formation of micelle-like assemblies that conferred colloidal stability and facilitated drug encapsulation. PZB-NS demonstrated 23-fold increase in kinetic solubility and accelerated dissolution achieving nearly complete drug release under both acidic (pH 1.2) and neutral (pH 6.8) conditions. Further, <i>in-vivo</i> pharmacokinetic evaluation was conducted in male Wistar rats and demonstrated a five-fold enhancement in systemic exposure as compared to crystalline PZB with no crystallization events. Taken together this is the first report describing a polymer-surfactant stabilized amorphous nanosuspension of PZB that offers a synergistic platform integrating solid-state pharmaceutics and nanotechnology so as to overcome biopharmaceutical barriers of challenging molecules.</p> Graphical Abstract <p></p>

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Polymer-Surfactant Stabilized Amorphous Nanosuspension of Pazopanib: Box-Behnken Optimization and In-vivo Evaluation

  • 期刊论文

  • 发表日期：

    2026年3月16日

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  • Vanshul Saini,
  • Ashish Hankare,
  • Prakash Amate,
  • Mehak Juneja,
  • Mahesh Kashyap,
  • Abhay T. Sangamwar

摘要

Pazopanib, a multitargeted tyrosine kinase inhibitor faces challenges at the formulation forefront due to high melting point, pH-dependent low aqueous solubility, in-vivo precipitation, low dissolution kinetics and, P-gp mediated drug efflux. To address these limitations an amorphous nanosuspension of Pazopanib (PZB-NS) was developed using an antisolvent precipitation approach with a dual stabilizer system comprising polyvinylpyrrolidone K-30 (PVP K-30) and Soluplus®. Formulation optimization was conducted using a Box-Behnken design (BBD) investigating critical process parameters such as polymer and surfactant concentrations, and solvent-to-antisolvent addition rate. The optimized nanosuspension exhibited a particle size of 123.9 ± 3.36 nm with 0.121 ± 0.002 PDI. The nano-formulation was further subjected to morphological characterization through PLM, SEM and PXRD that demonstrated amorphous transition of highly crystalline PZB. The FT-IR spectra revealed stabilizer-mediated hydrogen bonding and hydrophobic interactions while TEM micrographs depicted the formation of micelle-like assemblies that conferred colloidal stability and facilitated drug encapsulation. PZB-NS demonstrated 23-fold increase in kinetic solubility and accelerated dissolution achieving nearly complete drug release under both acidic (pH 1.2) and neutral (pH 6.8) conditions. Further, in-vivo pharmacokinetic evaluation was conducted in male Wistar rats and demonstrated a five-fold enhancement in systemic exposure as compared to crystalline PZB with no crystallization events. Taken together this is the first report describing a polymer-surfactant stabilized amorphous nanosuspension of PZB that offers a synergistic platform integrating solid-state pharmaceutics and nanotechnology so as to overcome biopharmaceutical barriers of challenging molecules.

Graphical Abstract